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Using ultralow light intensities that are well suited for investigating biological samples, we demonstrate whole-cell superresolution imaging by nonlinear structured-illumination microscopy. Structured-illumination microscopy can increase the spatial resolution of a wide-field light microscope by a factor of two, with greater resolution extension possible if the emission rate of the sample responds nonlinearly to the illumination intensity. Saturating the fluorophore excited state is one such nonlinear response, and a realization of this idea, saturated structured-illumination microscopy, has achieved approximately 50-nm resolution on dye-filled polystyrene beads. Unfortunately, because saturation requires extremely high light intensities that are likely to accelerate photobleaching and damage even fixed tissue, this implementation is of limited use for studying biological samples. Here, reversible photoswitching of a fluorescent protein provides the required nonlinearity at light intensities six orders of magnitude lower than those needed for saturation. We experimentally demonstrate approximately 40-nm resolution on purified microtubules labeled with the fluorescent photoswitchable protein Dronpa, and we visualize cellular structures by imaging the mammalian nuclear pore and actin cytoskeleton. As a result, nonlinear structured-illumination microscopy is now a biologically compatible superresolution imaging method.  相似文献   
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In this study, we investigated how adversities related to past and present morbidity, and genotype. Forty-two, suicide attempters and 22 matched control patients were followed-up after 13 years. Life-time adversities were explored in an interview, and the patients were reassessed psychiatrically. The serotonin-transporter-linked promotor region (5-HTTLPR) was typed. More adversities were reported by suicide attempters than controls, and by still-ill than recovered suicide attempters. Adversities reported at follow-up were related to psychiatric morbidity at follow-up, but not to morbidity 13 years earlier. The 5-HTTLPR, genotype was associated with reported adversities, but not chances of recovery. Adversities potentially affected chronic morbidity. 5-HTTLPR genotype did not affect long-term recovery.  相似文献   
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Studies have shown that female unpromoted general practice (GP) dentists have a taxing work situation with many problems related to their psychosocial work environment. This study aims to describe: 1) the participation of this group in organized network activity (support groups) in a region (Scania) in Sweden, 2) the sense of support compared with another organization and with a nationwide sample of GP dentists, and 3) the covariation of network participation with support. All unpromoted female dentists within the Public Dental Health Service (PDHS) in Scania received a questionnaire and 94% responded. Those participating in network activity ≥4 times a year constituted 12% of respondents. Cooperation between colleagues was lower than in the nationwide sample. Support from the PDHS was experienced as weak. It was not possible to explain why female unpromoted GP dentists participated ≥4 times a year, while those who felt lonely in their work were to a higher degree participants in a network. Almost 9 out of 10 reported being strengthened by the network both as a person and in a professional role. The female dentist was three times more likely to participate in a network if she had a male head of clinic. The main findings are a paucity of inter‐colleague contact and a lack of association between support and network participation. The many affirmative comments indicated that network participation might be a good coping strategy for unpromoted female GP dentists.  相似文献   
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